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microRNA and stem cell function

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Abstract

The identification and characterization of stem cells for various tissues has led to a greater understanding of development, tissue maintenance, and cancer pathology. Stem cells possess the ability to divide throughout their life and to produce differentiated daughter cells while maintaining a population of undifferentiated cells that remain in the stem cell niche and that retain stem cell identity. Many cancers also have small populations of cells with stem cell characteristics. These cells have been called cancer stem cells and are a likely cause of relapse in cancer patients. Understanding the biology of stem cells and cancer stem cells offers great promise in the fields of regenerative medicine and cancer treatment. microRNAs (miRNAs) are emerging as important regulators of post-transcriptional gene expression and are considered crucial for proper stem cell maintenance and function. miRNAs have also been strongly implicated in the development and pathology of cancer. In this review, we discuss the characteristics of various stem cell types, including cancer stem cells, and the importance of miRNAs therein.

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References

  • Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ, Clarke MF (2003) Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci USA 100:3983–3988

    PubMed  CAS  Google Scholar 

  • Aravin A, Gaidatzis D, Pfeffer S, Lagos-Quintana M, Landgraf P, Iovino N, Morris P, Brownstein MJ, Kuramochi-Miyagawa S, Nakano T, Chien M, Russo JJ, Ju J, Sheridan R, Sander C, Zavolan M, Tuschl T (2006) A novel class of small RNAs bind to MILI protein in mouse testes. Nature 442:203–207

    PubMed  CAS  Google Scholar 

  • Aravin AA, Sachidanandam R, Girard A, Fejes-Toth K, Hannon GJ (2007) Developmentally regulated piRNA clusters implicate MILI in transposon control. Science 316:744–747

    PubMed  CAS  Google Scholar 

  • Babaie Y, Herwig R, Greber B, Brink TC, Wruck W, Groth D, Lehrach H, Burdon T, Adjaye J (2007) Analysis of Oct4-dependent transcriptional networks regulating self-renewal and pluripotency in human embryonic stem cells. Stem Cells 25:500–510

    PubMed  CAS  Google Scholar 

  • Bar EE, Chaudhry A, Lin A, Fan X, Schreck K, Matsui W, Vescovi AL, Piccirillo S, Dimeco F, Olivi A, Eberhart CG (2007) Cyclopamine-mediated Hedgehog pathway inhibition depletes stem-like cancer cells in gioblastoma. Stem Cells 25:2524–2533

    PubMed  CAS  Google Scholar 

  • Behm-Ansmant I, Rehwinkel J, Doerks T, Stark A, Bork P, Izaurralde E (2006) mRNA degradation by miRNAs and GW182 requires both CCR4:NOT deadenylase and DCP1:DCP2 decapping complexes. Genes Dev 20:1885–1898

    PubMed  CAS  Google Scholar 

  • Bendall SC, Stewart MH, Menendez P, George D, Vijayaragavan K, Werbowetski-Ogilvie T, Ramos-Mejia V, Rouleau A, Yang J, Bosse M, Lajoie G, Bhatia M (2007) IGF and FGF cooperatively establish the regulatory stem cell niche of pluripotent human cells in vitro. Nature 448:1015–1021

    PubMed  CAS  Google Scholar 

  • Bernstein E, Caudy AA, Hammond SM, Hannon GJ (2001) Role for a bidentate ribonuclease in the initiation step of RNA interference. Nature 409:363–366

    PubMed  CAS  Google Scholar 

  • Bernstein E, Kim SY, Carmell MA, Murchison EP, Alcorn H, Li MZ, Mills AA, Elledge SJ, Anderson KV, Hannon GJ (2003) Dicer is essential for mouse development. Nat Genet 35:215–217

    PubMed  CAS  Google Scholar 

  • Bernstein BE, Mikkelsen TS, Xie X, Kamal M, Huebert DJ, Cuff J, Fry B, Meissner A, Wernig M, Plath K, Jaenisch R, Wagschal A, Feil R, Schreiber SL, Lander ES (2006) A bivalent chromatin structure marks key developmental genes in embryonic stem cells. Cell 125:315–326

    PubMed  CAS  Google Scholar 

  • Boiani M, Scholer HR (2005) Regulatory networks in embryo-derived pluripotent stem cells. Nat Rev Mol Cell Biol 6:872–884

    PubMed  CAS  Google Scholar 

  • Bonnet D, Dick JE (1997) Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat Med 3:730–737

    PubMed  CAS  Google Scholar 

  • Bottoni A, Piccin D, Tagliati F, Luchin A, Zatelli MC, degli Uberti EC (2005) miR-15a and miR-16–1 down-regulation in pituitary adenomas. J Cell Physiol 204:280–285

    PubMed  CAS  Google Scholar 

  • Boyer LA, Lee TI, Cole MF, Johnstone SE, Levine SS, Zucker JP, Guenther MG, Kumar RM, Murray HL, Jenner RG, Gifford DK, Melton DA, Jaenisch R, Young RA (2005) Core transcriptional regulatory circuitry in human embryonic stem cells. Cell 122:947–956

    PubMed  CAS  Google Scholar 

  • Cai X, Lu S, Zhang Z, Gonzalez CM, Damania B, Cullen BR (2005) Kaposi’s sarcoma-associated Herpes virus expresses an array of viral microRNAs in latently infected cells. Proc Natl Acad Sci USA 102:5570–5575

    PubMed  CAS  Google Scholar 

  • Cao X, Pfaff SL, Gage FH (2007) A functional study of miR-124 in the developing neural tube. Genes Dev 21:531–536

    PubMed  CAS  Google Scholar 

  • Chen D, McKearin D (2003) Dpp signaling silences Bam transcription directly to establish asymmetric divisions of germline stem cells. Curr Biol 13:1786–1791

    PubMed  CAS  Google Scholar 

  • Chen D, McKearin D (2005) Gene circuitry controlling a stem cell niche. Curr Biol 15:179–184

    PubMed  CAS  Google Scholar 

  • Chen CZ, Li L, Lodish HF, Bartel DP (2004) MicroRNAs modulate hematopoietic lineage differentiation. Science 303:83–86

    PubMed  CAS  Google Scholar 

  • Chen JF, Mandel EM, Thomson JM, Wu Q, Callis TE, Hammond SM, Conlon FL, Wang DZ (2006) The role of microRNA-1 and microRNA-133 in skeletal muscle proliferation and differentiation. Nat Genet 38:228–233

    PubMed  CAS  Google Scholar 

  • Cimmino A, Calin GA, Fabbri M, Iorio MV, Ferracin M, Shimizu M, Wojcik SE, Aqeilan RI, Zupo S, Dono M, Rassenti L, Alder H, Volinia S, Liu CG, Kipps TJ, Negrini M, Croce CM (2005) miR-15 and miR-16 induce apoptosis by targeting BCL2. Proc Natl Acad Sci USA 102:13944–13949

    PubMed  CAS  Google Scholar 

  • Collins AT, Berry PA, Hyde C, Stower MJ, Maitland NJ (2005) Prospective identification of tumorigenic prostate cancer stem cells. Cancer Res 65:10946–10951

    PubMed  CAS  Google Scholar 

  • Dalerba P, Dylla SJ, Park IK, Liu R, Wang X, Cho RW, Hoey T, Gurney A, Huang EH, Simeone DM, Shelton AA, Parmiani G, Castelli C, Clarke MF (2007) Phenotypic characterization of human colorectal cancer stem cells. Proc Natl Acad Sci USA 104:10158–10163

    PubMed  CAS  Google Scholar 

  • Dalmay T, Hamilton A, Rudd S, Angell S, Baulcombe DC (2000) An RNA-dependent RNA polymerase gene in Arabidopsis is required for posttranscriptional gene silencing mediated by a transgene but not by a virus. Cell 101:543–553

    PubMed  CAS  Google Scholar 

  • Dews M, Homayouni A, Yu D, Murphy D, Sevignani C, Wentzel E, Furth EE, Lee WM, Enders GH, Mendell JT, Thomas-Tikhonenko A (2006) Augmentation of tumor angiogenesis by a Myc-activated microRNA cluster. Nat Genet 38:1060–1065

    PubMed  CAS  Google Scholar 

  • Donnelly DS, Krause DS (2001) Hematopoietic stem cells can be CD34+ or CD34. Leuk Lymphoma 40:221–234

    PubMed  CAS  Google Scholar 

  • Eisterer W, Jiang X, Christ O, Glimm H, Lee KH, Pang E, Lambie K, Shaw G, Holyoake TL, Petzer AL, Auewarakul C, Barnett MJ, Eaves CJ, Eaves AC (2005) Different subsets of primary chronic myeloid leukemia stem cells engraft immunodeficient mice and produce a model of the human disease. Leukemia 19:435–441

    PubMed  CAS  Google Scholar 

  • Elbashir SM, Lendeckel W, Tuschl T (2001) RNA interference is mediated by 21- and 22-nucleotide RNAs. Genes Dev 15:188–200

    PubMed  CAS  Google Scholar 

  • Fan X, Matsui W, Khaki L, Stearns D, Chun J, Li YM, Eberhart CG (2006) Notch pathway inhibition depletes stem-like cells and blocks engraftment in embryonal brain tumors. Cancer Res 66:7445–7452

    PubMed  CAS  Google Scholar 

  • Fang D, Nguyen TK, Leishear K, Finko R, Kulp AN, Hotz S, Van Belle PA, Xu X, Elder DE, Herlyn M (2005) A tumorigenic subpopulation with stem cell properties in melanomas. Cancer Res 65:9328–9337

    PubMed  CAS  Google Scholar 

  • Forstemann K, Horwich MD, Wee L, Tomari Y, Zamore PD (2007) Drosophila microRNAs are sorted into functionally distinct Argonaute complexes after production by Dicer-1. Cell 130:287–297

    PubMed  Google Scholar 

  • Fuchs EJ, Whartenby KA (2004) Hematopoietic stem cell transplant as a platform for tumor immunotherapy. Curr Opin Mol Ther 6:48–53

    PubMed  CAS  Google Scholar 

  • Georgantas RW 3rd, Hildreth R, Morisot S, Alder J, Liu CG, Heimfeld S, Calin GA, Croce CM, Civin CI (2007) CD34+ hematopoietic stem-progenitor cell microRNA expression and function: a circuit diagram of differentiation control. Proc Natl Acad Sci USA 104:2750–2755

    PubMed  CAS  Google Scholar 

  • Gibbs CP, Kukekov VG, Reith JD, Tchigrinova O, Suslov ON, Scott EW, Ghivizzani SC, Ignatova TN, Steindler DA (2005) Stem-like cells in bone sarcomas: implications for tumorigenesis. Neoplasia 7:967–976

    PubMed  CAS  Google Scholar 

  • Giraldez AJ, Mishima Y, Rihel J, Grocock RJ, Van Dongen S, Inoue K, Enright AJ, Schier AF (2006) Zebrafish MiR-430 promotes deadenylation and clearance of maternal mRNAs. Science 312:75–79

    PubMed  CAS  Google Scholar 

  • Goodman JW, Hodgson GS (1962) Evidence for stem cells in the peripheral blood of mice. Blood 19:702–714

    PubMed  CAS  Google Scholar 

  • Greber B, Lehrach H, Adjaye J (2007) Silencing of core transcription factors in human EC cells highlights the importance of autocrine FGF signaling for self-renewal. BMC Dev Biol 7:46

    PubMed  Google Scholar 

  • Grivna ST, Pyhtila B, Lin H (2006) MIWI associates with translational machinery and PIWI-interacting RNAs (piRNAs) in regulating spermatogenesis. Proc Natl Acad Sci USA 103:13415–13420

    PubMed  CAS  Google Scholar 

  • Gu G, Yuan J, Wills M, Kasper S (2007) Prostate cancer cells with stem cell characteristics reconstitute the original human tumor in vivo. Cancer Res 67:4807–4815

    PubMed  CAS  Google Scholar 

  • Hammond SM, Bernstein E, Beach D, Hannon GJ (2000) An RNA-directed nuclease mediates post-transcriptional gene silencing in Drosophila cells. Nature 404:293–296

    PubMed  CAS  Google Scholar 

  • Hammond SM, Boettcher S, Caudy AA, Kobayashi R, Hannon GJ (2001a) Argonaute2, a link between genetic and biochemical analyses of RNAi. Science 293:1146–1150

    PubMed  CAS  Google Scholar 

  • Hammond SM, Caudy AA, Hannon GJ (2001b) Post-transcriptional gene silencing by double-stranded RNA. Nat Rev Genet 2:110–119

    PubMed  CAS  Google Scholar 

  • Han J, Lee Y, Yeom KH, Kim YK, Jin H, Kim VN (2004) The Drosha-DGCR8 complex in primary microRNA processing. Genes Dev 18:3016–3027

    PubMed  CAS  Google Scholar 

  • Hatfield SD, Shcherbata HR, Fischer KA, Nakahara K, Carthew RW, Ruohola-Baker H (2005) Stem cell division is regulated by the microRNA pathway. Nature 435:974–978

    PubMed  CAS  Google Scholar 

  • Hatfield S, Shcherbata HR, Ward EJ, Reynolds S, Ruohola-Baker H (2007) Clarke N, Sanseau P (eds) MicroRNAs and their involvement in stem cell division, in microRNAs; biology, function and expression

  • Hayashita Y, Osada H, Tatematsu Y, Yamada H, Yanagisawa K, Tomida S, Yatabe Y, Kawahara K, Sekido Y, Takahashi T (2005) A polycistronic microRNA cluster, miR-17–92, is overexpressed in human lung cancers and enhances cell proliferation. Cancer Res 65:9628–9632

    PubMed  CAS  Google Scholar 

  • He H, Jazdzewski K, Li W, Liyanarachchi S, Nagy R, Volinia S, Calin GA, Liu CG, Franssila K, Suster S, Kloos RT, Croce CM, de la Chapelle A (2005a) The role of microRNA genes in papillary thyroid carcinoma. Proc Natl Acad Sci USA 102:19075–19080

    PubMed  CAS  Google Scholar 

  • He L, Thomson JM, Hemann MT, Hernando-Monge E, Mu D, Goodson S, Powers S, Cordon-Cardo C, Lowe SW, Hannon GJ, Hammond SM (2005b) A microRNA polycistron as a potential human oncogene. Nature 435:828–833

    PubMed  CAS  Google Scholar 

  • Hirschmann-Jax C, Foster AE, Wulf GG, Nuchtern JG, Jax TW, Gobel U, Goodell MA, Brenner MK (2004) A distinct “side population” of cells with high drug efflux capacity in human tumor cells. Proc Natl Acad Sci USA 101:14228–14233

    PubMed  CAS  Google Scholar 

  • Ho MM, Ng AV, Lam S, Hung JY (2007) Side population in human lung cancer cell lines and tumors is enriched with stem-like cancer cells. Cancer Res 67:4827–4833

    PubMed  CAS  Google Scholar 

  • Hope KJ, Jin L, Dick JE (2004) Acute myeloid leukemia originates from a hierarchy of leukemic stem cell classes that differ in self-renewal capacity. Nat Immunol 5:738–743

    PubMed  CAS  Google Scholar 

  • Horwich MD, Li C, Matranga C, Vagin V, Farley G, Wang P, Zamore PD (2007) The Drosophila RNA methyltransferase, DmHen1, modifies germline piRNAs and single-stranded siRNAs in RISC. Curr Biol 17:1265–1272

    PubMed  CAS  Google Scholar 

  • Hossain A, Kuo MT, Saunders GF (2006) Mir-17–5p regulates breast cancer cell proliferation by inhibiting translation of AIB1 mRNA. Mol Cell Biol 26:8191–8201

    PubMed  CAS  Google Scholar 

  • Houbaviy HB, Murray MF, Sharp PA (2003) Embryonic stem cell-specific microRNAs. Dev Cell 5:351–358

    PubMed  CAS  Google Scholar 

  • Jin Z, Xie T (2007) Dcr-1 maintains Drosophila ovarian stem cells. Curr Biol 17:539–544

    PubMed  CAS  Google Scholar 

  • Kanellopoulou C, Muljo SA, Kung AL, Ganesan S, Drapkin R, Jenuwein T, Livingston DM, Rajewsky K (2005) Dicer-deficient mouse embryonic stem cells are defective in differentiation and centromeric silencing. Genes Dev 19:489–501

    PubMed  CAS  Google Scholar 

  • Keller G, Kennedy M, Papayannopoulou T, Wiles MV (1993) Hematopoietic commitment during embryonic stem cell differentiation in culture. Mol Cell Biol 13:473–486

    PubMed  CAS  Google Scholar 

  • Kennedy M, Keller GM (2003) Hematopoietic commitment of ES cells in culture. Methods Enzymol 365:39–59

    Article  PubMed  Google Scholar 

  • Kilpatrick TJ, Bartlett PF (1993) Cloning and growth of multipotential neural precursors: requirements for proliferation and differentiation. Neuron 10:255–265

    PubMed  CAS  Google Scholar 

  • Kim CF, Jackson EL, Woolfenden AE, Lawrence S, Babar I, Vogel S, Crowley D, Bronson RT, Jacks T (2005) Identification of bronchioalveolar stem cells in normal lung and lung cancer. Cell 121:823–835

    PubMed  CAS  Google Scholar 

  • Krutzfeldt J, Rajewsky N, Braich R, Rajeev KG, Tuschl T, Manoharan M, Stoffel M (2005) Silencing of microRNAs in vivo with “antagomirs”. Nature 438:685–689

    PubMed  Google Scholar 

  • Lai EC (2002) Micro RNAs are complementary to 3′UTR sequence motifs that mediate negative post-transcriptional regulation. Nat Genet 30:363–364

    PubMed  CAS  Google Scholar 

  • Lau NC, Seto AG, Kim J, Kuramochi-Miyagawa S, Nakano T, Bartel DP, Kingston RE (2006) Characterization of the piRNA complex from rat testes. Science 313:363–367

    PubMed  CAS  Google Scholar 

  • Lee RC, Feinbaum RL, Ambros V (1993) The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell 75:843–854

    PubMed  CAS  Google Scholar 

  • Lee Y, Ahn C, Han J, Choi H, Kim J, Yim J, Lee J, Provost P, Radmark O, Kim S, Kim VN (2003) The nuclear RNase III Drosha initiates microRNA processing. Nature 425:415–419

    PubMed  CAS  Google Scholar 

  • Lee YS, Nakahara K, Pham JW, Kim K, He Z, Sontheimer EJ, Carthew RW (2004) Distinct roles for Drosophila Dicer-1 and Dicer-2 in the siRNA/miRNA silencing pathways. Cell 117:69–81

    PubMed  CAS  Google Scholar 

  • Li CL, Johnson GR (1995) Murine hematopoietic stem and progenitor cells. I. Enrichment and biologic characterization. Blood 85:1472–1479

    PubMed  CAS  Google Scholar 

  • Li C, Heidt DG, Dalerba P, Burant CF, Zhang L, Adsay V, Wicha M, Clarke MF, Simeone DM (2007) Identification of pancreatic cancer stem cells. Cancer Res 67:1030–1037

    PubMed  CAS  Google Scholar 

  • Liu J, Carmell MA, Rivas FV, Marsden CG, Thomson JM, Song JJ, Hammond SM, Joshua-Tor L, Hannon GJ (2004) Argonaute2 is the catalytic engine of mammalian RNAi. Science 305:1437–1441

    PubMed  CAS  Google Scholar 

  • Llave C, Xie Z, Kasschau KD, Carrington JC (2002) Cleavage of Scarecrow-like mRNA targets directed by a class of Arabidopsis miRNA. Science 297:2053–2056

    PubMed  CAS  Google Scholar 

  • Loh YH, Wu Q, Chew JL, Vega VB, Zhang W, Chen X, Bourque G, George J, Leong B, Liu J, Wong KY, Sung KW, Lee CW, Zhao XD, Chiu KP, Lipovich L, Kuznetsov VA, Robson P, Stanton LW, Wei CL, Ruan Y, Lim B, Ng HH (2006) The Oct4 and Nanog transcription network regulates pluripotency in mouse embryonic stem cells. Nat Genet 38:431–440

    PubMed  CAS  Google Scholar 

  • Lujambio A, Ropero S, Ballestar E, Fraga MF, Cerrato C, Setien F, Casado S, Suarez-Gauthier A, Sanchez-Cespedes M, Git A, Spiteri I, Das PP, Caldas C, Miska E, Esteller M (2007) Genetic unmasking of an epigenetically silenced microRNA in human cancer cells. Cancer Res 67:1424–1429

    PubMed  CAS  Google Scholar 

  • Maines JZ, Park JK, Williams M, McKearin DM (2007) Stonewalling Drosophila stem cell differentiation by epigenetic controls. Development 134:1471–1479

    PubMed  CAS  Google Scholar 

  • Makeyev EV, Zhang J, Carrasco MA, Maniatis T (2007) The microRNA miR-124 promotes neuronal differentiation by triggering brain-specific alternative pre-mRNA splicing. Mol Cell 27(3):435–448, August 3

    PubMed  CAS  Google Scholar 

  • Martin GR (1981) Isolation of a pluripotent cell line from early mouse embryos cultured in medium conditioned by teratocarcinoma stem cells. Proc Natl Acad Sci USA 78:7634–7638

    PubMed  CAS  Google Scholar 

  • McKinstry WJ, Li CL, Rasko JE, Nicola NA, Johnson GR, Metcalf D (1997) Cytokine receptor expression on hematopoietic stem and progenitor cells. Blood 89:65–71

    PubMed  CAS  Google Scholar 

  • Meister G, Landthaler M, Patkaniowska A, Dorsett Y, Teng G, Tuschl T (2004) Human Argonaute2 mediates RNA cleavage targeted by miRNAs and siRNAs. Mol Cell 15:185–197

    PubMed  CAS  Google Scholar 

  • Meshorer E, Yellajoshula D, George E, Scambler PJ, Brown DT, Misteli T (2006) Hyperdynamic plasticity of chromatin proteins in pluripotent embryonic stem cells. Dev Cell 10:105–116

    PubMed  CAS  Google Scholar 

  • Miyoshi K, Tsukumo H, Nagami T, Siomi H, Siomi MC (2005) Slicer function of Drosophila Argonautes and its involvement in RISC formation. Genes Dev 19:2837–2848

    PubMed  CAS  Google Scholar 

  • Molnar A, Schwach F, Studholme DJ, Thuenemann EC, Baulcombe DC (2007) miRNAs control gene expression in the single-cell alga Chlamydomonas reinhardtii. Nature 447:1126–1129

    PubMed  CAS  Google Scholar 

  • Moorthy PP, Kumar AA, Devaraj H (2005) Expression of the Gas7 gene and Oct4 in embryonic stem cells of mice. Stem Cells Dev 14:664–670

    PubMed  CAS  Google Scholar 

  • Morshead CM, Reynolds BA, Craig CG, McBurney MW, Staines WA, Morassutti D, Weiss S, van der Kooy D (1994) Neural stem cells in the adult mammalian forebrain: a relatively quiescent subpopulation of subependymal cells. Neuron 13:1071–1082

    PubMed  CAS  Google Scholar 

  • Mossman AK, Sourris K, Ng E, Stanley EG, Elefanty AG (2005) Mixl1 and oct4 proteins are transiently co-expressed in differentiating mouse and human embryonic stem cells. Stem Cells Dev 14:656–663

    PubMed  CAS  Google Scholar 

  • Motamedi MR, Verdel A, Colmenares SU, Gerber SA, Gygi SP, Moazed D (2004) Two RNAi complexes, RITS and RDRC, physically interact and localize to noncoding centromeric RNAs. Cell 119:789–802

    PubMed  CAS  Google Scholar 

  • Mott JL, Kobayashi S, Bronk SF, Gores GJ (2007) mir-29 regulates Mcl-1 protein expression and apoptosis. Oncogene 26:6133–6140

    PubMed  CAS  Google Scholar 

  • Murchison EP, Partridge JF, Tam OH, Cheloufi S, Hannon GJ (2005) Characterization of Dicer-deficient murine embryonic stem cells. Proc Natl Acad Sci USA 102:12135–12140

    PubMed  CAS  Google Scholar 

  • Nichols J, Zevnik B, Anastassiadis K, Niwa H, Klewe-Nebenius D, Chambers I, Scholer H, Smith A (1998) Formation of pluripotent stem cells in the mammalian embryo depends on the POU transcription factor Oct4. Cell 95:379–391

    PubMed  CAS  Google Scholar 

  • Niwa H (2007) How is pluripotency determined and maintained? Development 134:635–646

    PubMed  CAS  Google Scholar 

  • O’Brien CA, Pollett A, Gallinger S, Dick JE (2007) A human colon cancer cell capable of initiating tumour growth in immunodeficient mice. Nature 445:106–110

    PubMed  CAS  Google Scholar 

  • Okamura K, Ishizuka A, Siomi H, Siomi MC (2004) Distinct roles for Argonaute proteins in small RNA-directed RNA cleavage pathways. Genes Dev 18:1655–1666

    PubMed  CAS  Google Scholar 

  • Okita K, Ichisaka T, Yamanaka S (2007) Generation of germline-competent induced pluripotent stem cells. Nature 448:313–317

    PubMed  CAS  Google Scholar 

  • Olsen PH, Ambros V (1999) The lin-4 regulatory RNA controls developmental timing in Caenorhabditis elegans by blocking LIN-14 protein synthesis after the initiation of translation. Dev Biol 216:671–680

    PubMed  CAS  Google Scholar 

  • Pal-Bhadra M, Leibovitch BA, Gandhi SG, Rao M, Bhadra U, Birchler JA, Elgin SC (2004) Heterochromatic silencing and HP1 localization in Drosophila are dependent on the RNAi machinery. Science 303:669–672

    PubMed  CAS  Google Scholar 

  • Park JK, Liu X, Strauss TJ, McKearin DM, Liu Q (2007) The miRNA pathway intrinsically controls self-renewal of Drosophila germline stem cells. Curr Biol 17:533–538

    PubMed  CAS  Google Scholar 

  • Patrawala L, Calhoun T, Schneider-Broussard R, Li H, Bhatia B, Tang S, Reilly JG, Chandra D, Zhou J, Claypool K, Coghlan L, Tang DG (2006) Highly purified CD44+ prostate cancer cells from xenograft human tumors are enriched in tumorigenic and metastatic progenitor cells. Oncogene 25:1696–1708

    PubMed  CAS  Google Scholar 

  • Phillips RL, Ernst RE, Brunk B, Ivanova N, Mahan MA, Deanehan JK, Moore KA, Overton GC, Lemischka IR (2000) The genetic program of hematopoietic stem cells. Science 288:1635–1640

    PubMed  CAS  Google Scholar 

  • Politz JC, Zhang F, Pederson T (2006) MicroRNA-206 colocalizes with ribosome-rich regions in both the nucleolus and cytoplasm of rat myogenic cells. Proc Natl Acad Sci USA 103:18957–18962

    PubMed  CAS  Google Scholar 

  • Prince ME, Sivanandan R, Kaczorowski A, Wolf GT, Kaplan MJ, Dalerba P, Weissman IL, Clarke MF, Ailles LE (2007) Identification of a subpopulation of cells with cancer stem cell properties in head and neck squamous cell carcinoma. Proc Natl Acad Sci USA 104:973–978

    PubMed  CAS  Google Scholar 

  • Ricci-Vitiani L, Lombardi DG, Pilozzi E, Biffoni M, Todaro M, Peschle C, De Maria R (2007) Identification and expansion of human colon-cancer-initiating cells. Nature 445:111–115

    PubMed  CAS  Google Scholar 

  • Rodriguez A, Griffiths-Jones S, Ashurst JL, Bradley A (2004) Identification of mammalian microRNA host genes and transcription units. Genome Res 14:1902–1910

    PubMed  CAS  Google Scholar 

  • Ruby JG, Jan CH, Bartel DP (2007) Intronic microRNA precursors that bypass Drosha processing. Nature 448:83–86

    PubMed  CAS  Google Scholar 

  • Saito K, Sakaguchi Y, Suzuki T, Suzuki T, Siomi H, Siomi MC (2007) Pimet, the Drosophila homolog of HEN1, mediates 2′-O-methylation of Piwi- interacting RNAs at their 3′ ends. Genes Dev 21:1603–1608

    PubMed  CAS  Google Scholar 

  • Sevignani C, Calin GA, Nnadi SC, Shimizu M, Davuluri RV, Hyslop T, Demant P, Croce CM, Siracusa LD (2007) MicroRNA genes are frequently located near mouse cancer susceptibility loci. Proc Natl Acad Sci USA 104:8017–8022

    PubMed  CAS  Google Scholar 

  • Si ML, Zhu S, Wu H, Lu Z, Wu F, Mo YY (2007) miR-21-mediated tumor growth. Oncogene 26:2799–2803

    PubMed  CAS  Google Scholar 

  • Singh SK, Hawkins C, Clarke ID, Squire JA, Bayani J, Hide T, Henkelman RM, Cusimano MD, Dirks PB (2004) Identification of human brain tumour initiating cells. Nature 432:396–401

    PubMed  CAS  Google Scholar 

  • Sitnicka E, Buza-Vidas N, Larsson S, Nygren JM, Liuba K, Jacobsen SE (2003) Human CD34+ hematopoietic stem cells capable of multilineage engrafting NOD/SCID mice express flt3: distinct flt3 and c-kit expression and response patterns on mouse and candidate human hematopoietic stem cells. Blood 102:881–886

    PubMed  CAS  Google Scholar 

  • Slack FJ, Basson M, Liu Z, Ambros V, Horvitz HR, Ruvkun G (2000) The lin-41 RBCC gene acts in the C. elegans heterochronic pathway between the let-7 regulatory RNA and the LIN-29 transcription factor. Mol Cell 5:659–669

    PubMed  CAS  Google Scholar 

  • Smardon A, Spoerke JM, Stacey SC, Klein ME, Mackin N, Maine EM (2000) EGO-1 is related to RNA-directed RNA polymerase and functions in germ-line development and RNA interference in C. elegans. Curr Biol 10:169–178

    PubMed  CAS  Google Scholar 

  • Song JJ, Smith SK, Hannon GJ, Joshua-Tor L (2004a) Crystal structure of Argonaute and its implications for RISC slicer activity. Science 305:1434–1437

    PubMed  CAS  Google Scholar 

  • Song X, Wong MD, Kawase E, Xi R, Ding BC, McCarthy JJ, Xie T (2004b) Bmp signals from niche cells directly repress transcription of a differentiation-promoting gene, bag of marbles, in germline stem cells in the Drosophila ovary. Development 131:1353–1364

    PubMed  CAS  Google Scholar 

  • Song X, Call GB, Kirilly D, Xie T (2007) Notch signaling controls germline stem cell niche formation in the Drosophila ovary. Development 134:1071–1080

    PubMed  CAS  Google Scholar 

  • Suh MR, Lee Y, Kim JY, Kim SK, Moon SH, Lee JY, Cha KY, Chung HM, Yoon HS, Moon SY, Kim VN, Kim KS (2004) Human embryonic stem cells express a unique set of microRNAs. Dev Biol 270:488–498

    PubMed  CAS  Google Scholar 

  • Szakmary A, Cox DN, Wang Z, Lin H (2005) Regulatory relationship among piwi, pumilio, and bag-of-marbles in Drosophila germline stem cell self-renewal and differentiation. Curr Biol 15:171–178

    PubMed  CAS  Google Scholar 

  • Tai MH, Chang CC, Kiupel M, Webster JD, Olson LK, Trosko JE (2005) Oct4 expression in adult human stem cells: evidence in support of the stem cell theory of carcinogenesis. Carcinogenesis 26:495–502

    PubMed  CAS  Google Scholar 

  • Takahashi K, Yamanaka S (2006) Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126:663–676

    PubMed  CAS  Google Scholar 

  • Tang C, Ang BT, Pervaiz S (2007) Cancer stem cell: target for anti-cancer therapy. FASEB J (in press)

  • Tran N, McLean T, Zhang X, Zhao CJ, Thomson JM, O’Brien C, Rose B (2007) MicroRNA expression profiles in head and neck cancer cell lines. Biochem Biophys Res Commun 358:12–17

    PubMed  CAS  Google Scholar 

  • Vagin VV, Sigova A, Li C, Seitz H, Gvozdev V, Zamore PD (2006) A distinct small RNA pathway silences selfish genetic elements in the germline. Science 313:320–324

    PubMed  CAS  Google Scholar 

  • Velkey JM, O’Shea KS (2003) Oct4 RNA interference induces trophectoderm differentiation in mouse embryonic stem cells. Genesis 37:18–24

    PubMed  CAS  Google Scholar 

  • Verdel A, Jia S, Gerber S, Sugiyama T, Gygi S, Grewal SI, Moazed D (2004) RNAi-mediated targeting of heterochromatin by the RITS complex. Science 303:672–676

    PubMed  CAS  Google Scholar 

  • Visvanathan J, Lee S, Lee B, Lee JW, Lee SK (2007) The microRNA miR-124 antagonizes the anti-neural REST/SCP1 pathway during embryonic CNS development. Genes Dev 21(7):744–749, April 1

    PubMed  CAS  Google Scholar 

  • Voorhoeve PM, le Sage C, Schrier M, Gillis AJ, Stoop H, Nagel R, Liu YP, van Duijse J, Drost J, Griekspoor A, Zlotorynski E, Yabuta N, De Vita G, Nojima H, Looijenga LH, Agami R (2006) A genetic screen implicates miRNA-372 and miRNA-373 as oncogenes in testicular germ cell tumors. Cell 124:1169–1181

    PubMed  CAS  Google Scholar 

  • Wakiyama M, Takimoto K, Ohara O, Yokoyama S (2007) Let-7 microRNA-mediated mRNA deadenylation and translational repression in a mammalian cell-free system. Genes Dev 21:1857–1862

    PubMed  CAS  Google Scholar 

  • Wang L, Li L, Menendez P, Cerdan C, Bhatia M (2005) Human embryonic stem cells maintained in the absence of mouse embryonic fibroblasts or conditioned media are capable of hematopoietic development. Blood 105:4598–4603

    PubMed  CAS  Google Scholar 

  • Wang J, Guo LP, Chen LZ, Zeng YX, Lu SH (2007) Identification of cancer stem cell-like side population cells in human nasopharyngeal carcinoma cell line. Cancer Res 67:3716–3724

    PubMed  CAS  Google Scholar 

  • Ward EJ, Shcherbata HR, Reynolds SH, Fischer KA, Hatfield SD, Ruohola-Baker H (2006) Stem cells signal to the niche through the Notch pathway in the Drosophila ovary. Curr Biol 16:2352–2358

    PubMed  CAS  Google Scholar 

  • Wernig M, Meissner A, Foreman R, Brambrink T, Ku M, Hochedlinger K, Bernstein BE, Jaenisch R (2007) In vitro reprogramming of fibroblasts into a pluripotent ES-cell-like state. Nature 448:318–324

    PubMed  CAS  Google Scholar 

  • Wiles MV, Keller G (1991) Multiple hematopoietic lineages develop from embryonic stem (ES) cells in culture. Development 111:259–267

    PubMed  CAS  Google Scholar 

  • Williams BP, Read J, Price J (1991) The generation of neurons and oligodendrocytes from a common precursor cell. Neuron 7:685–693

    PubMed  CAS  Google Scholar 

  • Wulczyn FG, Smirnova L, Rybak A, Brandt C, Kwidzinski E, Ninnemann O, Strehle M, Seiler A, Schumacher S, Nitsch R (2007) Post-transcriptional regulation of the let-7 microRNA during neural cell specification. FASEB J 21:415–426

    PubMed  CAS  Google Scholar 

  • Xi R, Xie T (2005) Stem cell self-renewal controlled by chromatin remodeling factors. Science 310:1487–1489

    PubMed  CAS  Google Scholar 

  • Yang Z, Ebright YW, Yu B, Chen X (2006) HEN1 recognizes 21–24 nt small RNA duplexes and deposits a methyl group onto the 2′ OH of the 3′ terminal nucleotide. Nucleic Acids Res 34:667–675

    PubMed  CAS  Google Scholar 

  • Yekta S, Shih IH, Bartel DP (2004) MicroRNA-directed cleavage of HOXB8 mRNA. Science 304:594–596

    PubMed  CAS  Google Scholar 

  • Yuan X, Curtin J, Xiong Y, Liu G, Waschsmann-Hogiu S, Farkas DL, Black KL, Yu JS (2004) Isolation of cancer stem cells from adult glioblastoma multiforme. Oncogene 23:9392–9400

    PubMed  CAS  Google Scholar 

  • Zhao L, Kim Y, Dinh TT, Chen X (2007a) miR172 regulates stem cell fate and defines the inner boundary of APETALA3 and PISTILLATA expression domain in Arabidopsis floral meristems. Plant J 51:840–849

    Google Scholar 

  • Zhao T, Li G, Mi S, Li S, Hannon GJ, Wang XJ, Qi Y (2007b) A complex system of small RNAs in the unicellular green alga Chlamydomonas reinhardtii. Genes Dev 21:1190–1203

    PubMed  CAS  Google Scholar 

  • Zheng X, Shen G, Yang X, Liu W (2007) Most C6 cells are cancer stem cells: evidence from clonal and population analyses. Cancer Res 67:3691–3697

    PubMed  CAS  Google Scholar 

  • Zhu S, Si ML, Wu H, Mo YY (2007) MicroRNA-21 targets the tumor suppressor gene tropomyosin 1 (TPM1). J Biol Chem 282:14328–14336

    PubMed  CAS  Google Scholar 

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  1. Department of Biochemistry, Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA, 98195, USA

    Steven Hatfield & Hannele Ruohola-Baker

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  1. Steven Hatfield
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  2. Hannele Ruohola-Baker
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Correspondence to Hannele Ruohola-Baker.

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Hatfield, S., Ruohola-Baker, H. microRNA and stem cell function. Cell Tissue Res 331, 57–66 (2008). https://doi.org/10.1007/s00441-007-0530-3

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